Two active oncogenes related to v-raf have been identified in both mouse and man. c-raf-1 has been localized to mouse chromosome 6 and to human chromosome 3p25 near sites specifically altered in small cell lung carcinoma (SCLC), familial renal cell carcinoma, mixed parotid gland tumors, and ovarian cancer. The human c-raf-1 gene contains 16 coding exons and spans more than 40 Kbp. The human 3.4-Kb mRNA encodes a protein of 648 amino acids (73 Kd) and is expressed in most mouse tissues and cell lines (including SCLC cell lines) at various levels. c-raf-1 mRNA expression is unaffected by growth factors, growth inhibitors, and tumor promoters, suggesting that c-raf-1 performs basic cellular functions and regulation of its activity occurs at the translational or protein level. A-raf-1 has been localized to the X chromosome in both mouse and man. It represents the first active human oncogene on a sex chromosome and is located between p21-q11, near the locus for testicular feminization syndrome and Menkes syndrome. Although no specific alterations involving the X chromosome have been described, a role in certain rare X-linked lymphoproliferative diseases seems possible. The A-raf mRNA is 2.6 Kb in both mouse and man. It encodes a 606 amino acid protein (67.5 Kd) which shows 60% homology with c-raf-1, and it displays a more restricted pattern of tissue expression than c-raf-1, with highest levels in the epididymis and intestine, suggesting a cell type- specific function.